Study Finds Increased Incidence of Cardiovascular Disease Among Patients With Cancer

For patients with cancer, cardiovascular risk was increased, with investigators hypothesizing that there is a relation to altered expression of inflammation and coagulation-related proteins, according to a study published in the Journal of the American Heart Association.

Of the 379,944 patients in the study, 65,047 were diagnosed with cancer during follow-up. For patients with cancer, higher mortality from cardiovascular disease (CVD; P <.0001), higher atherosclerotic CVD (ASCVD)-related death (P <.0001), and higher all-cause death (P <.0001) were noted. In the multivariate Cox analysis, cancer was noted as a statistically significant risk factor for CVD death.

Patients with cancer had an increased risk of cardiovascular death (HR, 2.46; 95% CI, 2.30-2.63), ASCVD death (HR, 2.10; 95% CI, 1.93-2.30), and all-cause mortality (HR, 17.30; 95% CI, 16.88-17.73). After an adjustment that the investigators noted was rigorous, those with cancer remained at a high risk of cardiovascular death (adjusted HR [aHR], 1.50; 95% CI, 1.40-1.61), ASCVD death (aHR, 1.25; 95% CI, 1.14-1.37), and all-cause mortality (aHR, 12.17; 95% CI, 11.86-12.49).

A subgroup analysis showed that cardiovascular mortality was significantly associated with patients with cancer in all subgroups except for patients who were Black. When adjusting for confounders, including age (P <.001), sex (P = .001), smoking status (P = .003), hypertension (P <.001), and history of diabetes (P = .006), significant interactions were noted.

The subgroup analysis also highlighted that patients with cancer who did not have a history of hypertension (HR, 2.02; 95% CI, 1.81-2.25) compared with those who did not have cancer (HR, 1.49; 95% CI, 1.36-1.63), and those with cancer who did not have diabetes (HR, 1.74; 95% CI, 1.61-1.88) vs those without cancer (HR, 1.46; 95% CI, 1.24-1.70) had a higher risk of cardiovascular death.

There were 382 plasma proteins in the plasma proteomic analysis that were upregulated and 282 that were downregulated in those with cancer vs those without cancer. The genome-wide association studies (GWAS) analysis showed 70 variants in patients with cancer vs the controls. In the phenome-wide association study (PheWAS) analysis, the phenotypes with the closest relationships were cancer-related diseases, like hyperplasia of the prostate, prostate cancer, and malignant neoplasm. Additionally, 32 of the 70 variants were significantly associated with diseases aside from cancer, including cardiovascular, respiratory, and dermatological diseases.

“Our study concluded that patients with cancer have a higher risk of cardiovascular mortality compared with populations without cancer. Plasma proteomic analysis demonstrated that upregulated proteins in patients with cancer were enriched in pathways related to complement and coagulation, and inflammation. GWAS and PheWAS analyses revealed a close genetic connection between cancer and tumor‐related diseases, but few CVDs shared common genetic variants with cancer,” the study investigators wrote.

The mean age in patients with cancer was 59.71 years ± 7.05 vs 55.51 years ± 8.13 in patients without cancer (P <.001). For those with cancer, 47.6% were female and 52.3% were male; in those without cancer, 54.4% were female and 45.6% were male. Patients with and without cancer were either White (96.7% vs 93.2%, respectively), Asian (1.6% vs 3.7%), Black (0.3% vs 0.8%), mixed/other (0.8% vs 1.7%), or unknown (0.4% vs 0.6%). In the study, patients with and without cancer had never previously smoked (49.2% vs 56.0%) but were current alcohol users (92.4% vs 91.5%). In the study, the most frequent cancer types were skin (34.10%), prostate (13.50%), breast (12.90%), and gastrointestinal (12.90%).

The study found a higher risk of cardiovascular death for patients with cancer who were younger compared with those older than 75 years. Across all cancer types, there was an elevated risk of CVD and ASCVD mortality, with the highest risk being in lymphoma/other hematological cancers, head and neck, and breast. The cancers with the lowest risk were prostate, gastrointestinal, and lung.

For patients with breast and gynecological cancers, the cumulative incidence of CVD-related death was low. After a cancer diagnosis, the risk of CVD-related death increased during the first 3 years, then decreased gradually over the next 7 years.

“The increased cardiovascular risk in patients with cancer is primarily attributed to changes in the expression of inflammation‐ and coagulation‐related proteins. In clinical practice, greater attention should be given to managing endocrine, kidney, and inflammation‐related risk factors in the population with cancer,” the authors concluded.

Reference

Du Y, Han S, Cheng J, et al. Risk of cardiovascular disease mortality in patients with diagnosed cancer and associated genetic and proteomic mechanisms: A UK Biobank-based cohort study. J Am Heart Assoc. Published online December 30, 2025. doi:10.1161/JAHA.125.044826